Since NMDA receptor overactivation is implicated in excitotoxicity, NMDA receptor antagonists have held much promise for the treatment of conditions that involve excitotoxicity, including benzodiazepine withdrawal, traumatic brain injury, stroke, and neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's. (wikipedia.org)

It was one of the first selective 5-HT6 receptor antagonists to be discovered, and was found through high-throughput screening of the SmithKline Beecham Compound Bank using cloned 5-HT6 receptors as a target, with an initial lead compound being developed into SB-271046 through a structure-activity relationship (SAR) study. (wikipedia.org)

S-(−)-HA-966 has been described as a "γ-hydroxybutyric acid (GHB)-like agent" and a "potent y-butyrolactone-like sedative", but it shows no affinity for the GABAB receptor (GABABR). (wikipedia.org)

SB-271046 was found to be potent and selective in vitro and had good oral bioavailability in vivo, but had poor penetration across the blood-brain barrier, so further SAR work was then conducted, which led to improved 5-HT6 antagonists such as SB-357,134 and SB-399,885. (wikipedia.org)

Kynurenic acid was discovered in 1853 by the German chemist Justus von Liebig in dog urine, which it was apparently named after. (wikipedia.org)

However, recently (2011) direct recording of α7 nicotinic acetylcholine receptor currents in adult (noncultured) hippocampal interneurons by the Cooper laboratory validated a 2009 study that failed to find any blocking effect of kynurenic acid across a wide range of concentrations, thus suggesting that in noncultured, intact preparations from adult animals there is no effect of kynurenic acid on α7 nicotinic acetylcholine receptor currents. (wikipedia.org)

High levels of kynurenic acid have been identified in patients suffering from tick-borne encephalitis, schizophrenia and HIV-related illnesses. (wikipedia.org)

A kynurenic acid hypothesis of schizophrenia was proposed in 2007, based on its action on midbrain dopamine activity and NMDArs, thus linking dopamine hypothesis of schizophrenia with the glutamate hypothesis of the disease. (wikipedia.org)

High levels of kynurenic acid have been identified in human urine in certain metabolic disorders, such as marked pyridoxine deficiency and deficiency/absence of kynureninase. (wikipedia.org)

When researchers decreased the levels of kynurenic acid in the brains of mice, their cognition was shown to improve markedly. (wikipedia.org)

One controlled study kept mice on a ketogenic diet and measured kynurenic acid concentrations in different parts of the brain. (wikipedia.org)

It found that the mice on the ketogenic diet had greater kynurenic acid concentrations in the striatum and hippocampus compared to mice on a normal diet, with no significant difference in the cortex. (wikipedia.org)